Alexion Pharmaceuticals announced at the JP Morgan Healthcare Conference that it was planning to initiate a pivotal Phase III trial of Ultomiris (ravulizumab) in amyotrophic lateral sclerosis (ALS). The company’s chief executive officer, Ludwig Hantson, admits it’s a longshot.
“We are aware that this is a high-risk, high-reward program,” Hantson said.
Ultomiris is the first and only long-acting C5 inhibitor administered in adults every eight weeks for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) and for adults and children with atypical hemolytic uremic syndrome (aHUS).
The new study, a 50-week global trial called CHAMPION-ALS, will study about 350 adults with a primary endpoint of change in ALS functional rating scale-revised (ALSFRS-R) score. The company submitted the IND to the FDA in the fourth quarter of 2019 and expects to launch the new study this quarter.
“Given the significant need for new and improved treatments for ALS, we are committed to advancing this clinical program with urgency,” said John Orloff, executive vice president and head of Research & Development at Alexion. “Based on preclinical data and the significant role complement activation is known to play in other neuromuscular diseases, we believe Ultomiris has the potential to inhibit complement-mediated damage in people with ALS, which may slow disease progression.”
ALS is a neurological disease marked by progressive degeneration of motor neurons in the brain and spinal cord. When these nerve cells die, the brain can’t fire and control muscle movement, leading to severe disability, paralysis and eventually death.
Perhaps part of the reason Alexion is willing to swing at this difficult target is how successful Ultomiris has been. As of January 10, the drug had over 59% of the U.S. market for PNH who’d been previously taking the company’s Soliris. This is only a year after the launch of Ultomiris.
However, only a week ago, Waltham, Massachusetts-based Apellis Pharmaceuticals announced that its pegcetacoplan beat out Alexion’s Soliris in its Phase III PEGASUS study in adults with PNH.
PNH is a rare, chronic, life-threatening disease of the blood linked to abnormally low hemoglobin levels caused by the destruction of red blood cells. The PEGASUS study evaluated 80 adults with PNH, comparing pegcetacoplan to Alexion’s Soliris (eculizumab). Patients were required to have been on stable doses of Soliris for at least three months with a hemoglobin level of more than 10.5 g/dL at the screening visit. For four weeks, patients were dosed with 1,080 mg of pegcetacoplan twice a week in addition to their current dose of Soliris.
Ultomiris is basically Alexion’s replacement drug for Soliris. So this trial may be an attempt to extend the life of Ultomiris in the face of upcoming competition. On November 22, 2019, Alexion’s Soliris was approved in Japan for the prevention of relapse in patients with anti-aquaporin-4 (AQP4) antibody-positive neuromyelitis optica spectrum disorder (NMOSD), including neuromyelitis optica. NMOSD is a rare, devastating, complement-mediated disease of the central nervous system.
And on December 16, 2019, Alexion exercised its option for two additional complement-pathway drugs from Dicerna Pharmaceuticals. These are GalXC RNAi molecules. This is part of an existing research collaboration and license deal that now includes four complement compounds. Alexion paid Dicerna $10 million for each of the new compounds.
As part of its presentation at JPM, Alexion announced plans to introduce seven new products and have treatments for 16 diseases by 2023.
Jan 15, 2020